The interrelated disorders of obesity (O), metabolic syndrome (MS), type 2 diabetes mellitus (T2DM), and associated cardiovascular disorders rank amongst the most important health problems facing Western and Westernized populations. Clinical abnormalities in these disorders, including obesity, hyper/dyslipidemia, insulin resistance, and glucose intolerance are each independent cardiovascular risk factors that are usually treated piecemeal and with limited success. In insulin-resistant states of O/MS/T2DM, insulin effects on hepatic lipid synthesis are conserved, even when effects on hepatic glucose production are diminished, as in overt T2DM. This paradox in T2DM results in hyper/dyslipidemia and hyperglycemia, a lethal combination for developing cardiovascular disease.
New approaches are needed to contain the costly pandemic of O/MS/T2DM. Identifying a unifying pathogenetic factor for these risk factors that could serve as a single therapeutic target would simplify this task.